CORRESPONDENCE
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5. Mohsenifar Z, Horak D, Brown H, Koerner K. Sensitive indices of improvement in pulmonary rehabilitation programs. Chest 1983; 83:189-92.
ANTONIO PATESSIO, M.D. FRANCO Iotr, M.D. SILVIO ZANABONI, M.D. CLAUDIO DONNER, M.D. Division of Pulmonary Disease Clinica del Lavoro Foundation Medical Center for Rehabilitation, Veruno (NO), Italy
From the Authors: We welcome the opportunity to reinforce the message of our recent publication. The exercise prescription for patients with chronic obstructive pulmonary disease (COPD) (and indeed, the field of pulmonary rehabilitation) is greatly in need of a scientific basis. It was the aim of our work to determine whether physiologic principles of exercise training, which are applicable to normal subjects, are also applicable to patients with COPD. One of the central findings of this research is that the patients with COPD we studied experienced lactic acidosis at very low work rates. We hypothesize that this occurs because these patients are extremely sedentary, resulting in detrained muscles of locomotion and perhaps also because pulmonary vascular disease limits exercise cardiac output. In these patients, even a task engendering a V02 equivalent to a moderate walking pace produces lactic acidosis. Belman and Mohsenifar imply that the finding of an early lactic acidosis is not characteristic of patients with obstructive lung disease. Yet the two studies they cite (1, 2) show quite the opposite; in both studies, patients with COPD demonstrated substantially elevated blood lactate levels (averaging 3.5 mEq/L) in response to submaximal exercisetasks. In both studies, the averagelactate threshold was wellunder 1 L/min - quite similar to the range we observed. Another central finding of our study was that training intensity must be high in order to elicit a physiologic training effect manifested by a reduction in blood lactate. It is therefore not unexpected that the two studies cited failed to obtain an appreciable reduction in lactic acidosis as a result of the exercise program. Frequency and duration characteristics of the exercise programs were inferior to those of our study. More importantly, training intensity was based on heart rate criteria (2) or a fixed percentage of the maximally tolerated work rate (1). These strategies, although useful in healthy subjects or cardiac patients, have more recently been shown to yield inappropriately low exercise intensities for patients with COPD (3). Indeed, Belman himself has criticized the use of target heart rates to estimate training intensity for patients with COPD (4). Westudied a group of patients with a wide range of disease severity who were participating in a program of pulmonary rehabilitation. Though subjects with mild COPD are included, it makes no sense at all to suggest that their disease is "coincidental!" In fact, we find the Italian stress on rehabilitating patients while their lung disease does not preclude their return to a productive life a refreshing change from the American system, which mainly focuses on attempting to salvage severely ill patients. In the data we presented, we could detect no tendency for the degree of obstruction to determine the ability to achieve a physiologic training effect. We have since studied an additional 10 subjects who underwent a similarly rigorous program of exercise training. This was an older (average age = 61 years), more severely obstructed (average FEV I = 44% predicted) group than we previously studied. Yet,in response to identical heavy exercisetasks, blood lactate decreased from an average of 3.7 mEq/L to 2.6 mEq/L as a result of training, a sign that a physiologic training effect was achieved. Though we believe that further research is needed in this area, we feel that our findings point the way to new strategies for rehabilitative exercise prescription for many patients with COPD. RICHARD CASABURI, PH.D., M.D. KARLMAN WASSERMAN, M.D., PH.D. Division of Respiratory and Critical Care Physiology and Medicine Harbor-UCLA Medical Center Torrance, California
1. Mohsenifar Z, Horak D, Brown H, Koerner K. Sensitive indices of improvement in pulmonary rehabilitation programs. Chest 1983; 83:189-92. 2. Degre S, Sergysels R, Messin R, Vandermoten P, Salhadin P, Denolin P, et al. Hemodynamic responses to physical training in patients with chronic lung disease. Am Rev Respir Dis 1974; 110:395-402. 3. Ries AL, Archibald CJ. Endurance exercise training at maximal targets in patients with chronic obstructive pulmonary disease. J. Cardiopulmonary Rehabil 1987; 7:594-601. 4. Belman MJ. Exercise in chronic obstructive pulmonary disease. Clin Chest Med 1986; 7:585-97.
SIX-MONTHS ISONIAZID-RIFAMPIN TREATMENT FOR PULMONARY TUBERCUWSIS IN CHILDREN
To the Editor: In the November 1990 issue of the REVIEW, Reis and colleagues reported a study of 117 Brazilian children with pulmonary tuberculosis treated with 6 months of daily isoniazid (INH) and rifampin (RIF). In 1983, we reported our experience with a similar regimen in Arkansas (2). Of 120 children with hilar adenopathy as the only manifestation of primary tuberculosis seen between 1980and 1989, none was symptomatic. Reis and coworkers discuss the advantages of short course chemotherapy, which includes reduced cost of and toxicity from the medication and better compliance. However, they do not mention the further advantage of twice-weekly therapy in all of these areas to facilitate direct administration in uncooperative patients. Their article did not give any details on the monitoring of the therapy or any indication of how they determined compliance. Our treatment regimen of 1 month of daily INH and RIF followed by 8 months of these drugs administered twice weekly has been highly successful in Arkansas where the incidence of INH resistance is about 30/0. It is one of the officially approved treatment regimens for tuberculosis in areas of low incidence of INH resistance. Where incidence of INH resistance is higher the favored regimen involves INH and RIF with pyrazinamide (PZA) for 2 months, followed by 4 months of INH and RIF, which is usually given twice weekly (3). If the incidence of INH resistance is as high in Brazil as in other developing countries, therapy with only two drugs would, in fact, be single drug therapy, which few would find acceptable. In Arkansas, we have demonstrated very successful treatment of children with hilar adenopathy alone and even in adults with smearnegative pulmonary tuberculosis, including those with pleural effusion, with largely twice weekly INH and RIF for 6 months. Expense of therapy must be considered in this time of cost containment and particularly in third world countries. Using Arkansas costs, daily INH and RIF for 6 months for a 20 kg child would be $82.80 (180 doses). Six months of largely twice weekly INH and RIF (the Arkansas protocol) would cost $35.36 (74 doses) and the same regimen for 9 months, $48.10 (98 doses). The six-month regimen with PZA, INH, and RIF daily for 2 months and 4 months of twice weekly INH and RIF would cost $80.04 (96 doses); PZA contributes 44% ofthe cost. Biddulph (4) from New Guinea recently reported the successful use of this regimen for 639 cases of childhood tuberculosis and stated that the cost for the treatment of a 25 kg child, using the UNICEF price list, would be only $25. Kumar and coworkers in the same journal (5) reported a comparison of
1221
5. Mohsenifar Z, Horak D, Brown H, Koerner K. Sensitive indices of improvement in pulmonary rehabilitation programs. Chest 1983; 83:189-92.
ANTONIO PATESSIO, M.D. FRANCO Iotr, M.D. SILVIO ZANABONI, M.D. CLAUDIO DONNER, M.D. Division of Pulmonary Disease Clinica del Lavoro Foundation Medical Center for Rehabilitation, Veruno (NO), Italy
From the Authors: We welcome the opportunity to reinforce the message of our recent publication. The exercise prescription for patients with chronic obstructive pulmonary disease (COPD) (and indeed, the field of pulmonary rehabilitation) is greatly in need of a scientific basis. It was the aim of our work to determine whether physiologic principles of exercise training, which are applicable to normal subjects, are also applicable to patients with COPD. One of the central findings of this research is that the patients with COPD we studied experienced lactic acidosis at very low work rates. We hypothesize that this occurs because these patients are extremely sedentary, resulting in detrained muscles of locomotion and perhaps also because pulmonary vascular disease limits exercise cardiac output. In these patients, even a task engendering a V02 equivalent to a moderate walking pace produces lactic acidosis. Belman and Mohsenifar imply that the finding of an early lactic acidosis is not characteristic of patients with obstructive lung disease. Yet the two studies they cite (1, 2) show quite the opposite; in both studies, patients with COPD demonstrated substantially elevated blood lactate levels (averaging 3.5 mEq/L) in response to submaximal exercisetasks. In both studies, the averagelactate threshold was wellunder 1 L/min - quite similar to the range we observed. Another central finding of our study was that training intensity must be high in order to elicit a physiologic training effect manifested by a reduction in blood lactate. It is therefore not unexpected that the two studies cited failed to obtain an appreciable reduction in lactic acidosis as a result of the exercise program. Frequency and duration characteristics of the exercise programs were inferior to those of our study. More importantly, training intensity was based on heart rate criteria (2) or a fixed percentage of the maximally tolerated work rate (1). These strategies, although useful in healthy subjects or cardiac patients, have more recently been shown to yield inappropriately low exercise intensities for patients with COPD (3). Indeed, Belman himself has criticized the use of target heart rates to estimate training intensity for patients with COPD (4). Westudied a group of patients with a wide range of disease severity who were participating in a program of pulmonary rehabilitation. Though subjects with mild COPD are included, it makes no sense at all to suggest that their disease is "coincidental!" In fact, we find the Italian stress on rehabilitating patients while their lung disease does not preclude their return to a productive life a refreshing change from the American system, which mainly focuses on attempting to salvage severely ill patients. In the data we presented, we could detect no tendency for the degree of obstruction to determine the ability to achieve a physiologic training effect. We have since studied an additional 10 subjects who underwent a similarly rigorous program of exercise training. This was an older (average age = 61 years), more severely obstructed (average FEV I = 44% predicted) group than we previously studied. Yet,in response to identical heavy exercisetasks, blood lactate decreased from an average of 3.7 mEq/L to 2.6 mEq/L as a result of training, a sign that a physiologic training effect was achieved. Though we believe that further research is needed in this area, we feel that our findings point the way to new strategies for rehabilitative exercise prescription for many patients with COPD. RICHARD CASABURI, PH.D., M.D. KARLMAN WASSERMAN, M.D., PH.D. Division of Respiratory and Critical Care Physiology and Medicine Harbor-UCLA Medical Center Torrance, California
1. Mohsenifar Z, Horak D, Brown H, Koerner K. Sensitive indices of improvement in pulmonary rehabilitation programs. Chest 1983; 83:189-92. 2. Degre S, Sergysels R, Messin R, Vandermoten P, Salhadin P, Denolin P, et al. Hemodynamic responses to physical training in patients with chronic lung disease. Am Rev Respir Dis 1974; 110:395-402. 3. Ries AL, Archibald CJ. Endurance exercise training at maximal targets in patients with chronic obstructive pulmonary disease. J. Cardiopulmonary Rehabil 1987; 7:594-601. 4. Belman MJ. Exercise in chronic obstructive pulmonary disease. Clin Chest Med 1986; 7:585-97.
SIX-MONTHS ISONIAZID-RIFAMPIN TREATMENT FOR PULMONARY TUBERCUWSIS IN CHILDREN
To the Editor: In the November 1990 issue of the REVIEW, Reis and colleagues reported a study of 117 Brazilian children with pulmonary tuberculosis treated with 6 months of daily isoniazid (INH) and rifampin (RIF). In 1983, we reported our experience with a similar regimen in Arkansas (2). Of 120 children with hilar adenopathy as the only manifestation of primary tuberculosis seen between 1980and 1989, none was symptomatic. Reis and coworkers discuss the advantages of short course chemotherapy, which includes reduced cost of and toxicity from the medication and better compliance. However, they do not mention the further advantage of twice-weekly therapy in all of these areas to facilitate direct administration in uncooperative patients. Their article did not give any details on the monitoring of the therapy or any indication of how they determined compliance. Our treatment regimen of 1 month of daily INH and RIF followed by 8 months of these drugs administered twice weekly has been highly successful in Arkansas where the incidence of INH resistance is about 30/0. It is one of the officially approved treatment regimens for tuberculosis in areas of low incidence of INH resistance. Where incidence of INH resistance is higher the favored regimen involves INH and RIF with pyrazinamide (PZA) for 2 months, followed by 4 months of INH and RIF, which is usually given twice weekly (3). If the incidence of INH resistance is as high in Brazil as in other developing countries, therapy with only two drugs would, in fact, be single drug therapy, which few would find acceptable. In Arkansas, we have demonstrated very successful treatment of children with hilar adenopathy alone and even in adults with smearnegative pulmonary tuberculosis, including those with pleural effusion, with largely twice weekly INH and RIF for 6 months. Expense of therapy must be considered in this time of cost containment and particularly in third world countries. Using Arkansas costs, daily INH and RIF for 6 months for a 20 kg child would be $82.80 (180 doses). Six months of largely twice weekly INH and RIF (the Arkansas protocol) would cost $35.36 (74 doses) and the same regimen for 9 months, $48.10 (98 doses). The six-month regimen with PZA, INH, and RIF daily for 2 months and 4 months of twice weekly INH and RIF would cost $80.04 (96 doses); PZA contributes 44% ofthe cost. Biddulph (4) from New Guinea recently reported the successful use of this regimen for 639 cases of childhood tuberculosis and stated that the cost for the treatment of a 25 kg child, using the UNICEF price list, would be only $25. Kumar and coworkers in the same journal (5) reported a comparison of
